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Treatment of meningiomas refractory to surgery and irradiation is challenging and effective chemotherapies are still lacking. Recently, in vitro analyses revealed decitabine (DCT, 5-aza-2’–deoxycytidine) to be effective in high-grade meningiomas and, moreover, to induce hypomethylation of distinct oncogenes only sparsely described in meningiomas in vivo yet.Expression of the corresponding onco- and tumor suppressor genes TRIM58, FAM84B, ELOVL2, MAL2, LMO3, and DIO3 were analyzed and scored by immunohistochemical staining and RT-PCR in samples of 111 meningioma patients. Correlations with clinical and histological variables and prognosis were analyzed in uni- and multivariate analyses.All analyzed oncogenes were highly expressed in meningiomas. Expression scores of TRIM58 tended to be higher in benign than in high-grade tumors 20 vs 16 (p = .002) and all 9 samples lacking TRIM58 expression displayed WHO grade II/III histology. In contrast, median expression scores for both FAM84B (6 vs 4, p ≤ .001) and ELOVL2 (9 vs 6, p DIO3 expression was distinctly higher in all analyzed samples as compared to the reference decitabine-resistant Ben-Men 1 cell line. Increased ELOVL2 expression (score ≥ 8) correlated with tumor relapse in both uni- (HR: 2.42, 95%CI 1.18–4.94; p = .015) and multivariate (HR: 2.09, 95%CI 1.01–4.44; p = .046) analyses.All oncogenes involved in DCT efficacy in vitro are also widely expressed in vivo, and expression is partially associated with histology and prognosis. These results strongly encourage further analyses of DCT efficiency in meningiomas in vitro and in situ.

To assess the long-term hazard of tsunamis, particularly in regions with a short and fragmented historical record, sedimentary deposits of tsunamis are an essential tool. In the North Sea region, evidence of tsunamis is scarce. The Shetland Islands are an exception, as they contain abundant deposits of the Storegga tsunami (c. 8150 cal. a BP), and additionally more fragmented evidence of younger tsunami events c. 5500 and c. 1500 cal. a BP. Sediments of the youngest tsunami (the “Dury Voe” event) have only been found at two sites so far, marked by thin landward fining and landward thinning sand sheets which are vertically confined by peat. Here, we present sedimentary evidence for the youngest Shetland tsunami from the small coastal lake of Loch Flugarth, northern Mainland. Three gravity cores of up to 91.7 cm length were taken behind the barrier separating the lake from a shallow marine embayment. The cores show organic-rich background deposition with many sub-cm-scale sand layers, reflecting recurring storm overwash and a sediment source limited to the active beach and uppermost subtidal zone. A basal 13 cm-thick sand layer, dated to 426–787 cal. a CE based on 14C, 137Cs and Bayesian age-depth modelling, was found in all three cores. High-resolution grain-size analysis identified four normally graded sublayers with inversely graded traction carpets in the lower part of two sublayers. An organic-rich ‘mud’ drape and ‘mud’ cap cover the upper two sublayers, which also contain small rip-up clasts. Grain-size distributions show a difference between the basal sand layer and the coarser and better sorted thin storm layers. Principal component analysis of X-ray fluorescence core scanning data also distinguishes both sand units: Zr, Fe and Ti dominate the basal sand, while the thin storm layers are high in K and Si. The enrichment of the basal sand layer in Zr and Ti, in combination with increased magnetic susceptibility, may be related to higher heavy mineral content in the basal sand reflecting the additional marine sediment source of a tsunami deposit below the storm-wave base. Based on reinterpretation of chronological data from the two published sites and the chronostratigraphy of the present study, the Dury Voe tsunami seems to be slightly younger, i.e., closer to 1400 cal. a BP. Although the source of the tsunami remains unclear, the lack of evidence for this event outside of the Shetlands suggests that it was smaller than the older Storegga tsunami, which affected most of the North Sea basin.

The El Niño-Southern Oscillation (ENSO), known for exceptional heavy rainfalls, droughts and inundations in the Pacific and Indian Ocean realm, is one of the largest oceanic and atmospheric phenomena on Earth influencing global climate patterns. Over the last decades, a strong warming in the high latitudes of both hemispheres has been observed to coincide with the rise of a third ENSO type — “El Niño/La Niña Modoki”, also called Central Pacific ENSO. During El Niño Modoki (La Niña Modoki) events, sea-surface temperature (SST) is higher (lower) in the central equatorial Pacific, flanked by colder (warmer) SSTs in the western or eastern Pacific, associated with a twin Walker Circulation. The study aims to understand the underlying spatio-temporal dynamics and processes of Central Pacific ENSO and a possible link to anthropogenic impacts from a paleo-perspective to improve the predictability of Central Pacific ENSO variations in the future. Therefore, high-resolution (c. 1–2 kyr resolution) proxy records of SST variability are generated from marine sediment cores from the western, central, and eastern equatorial Pacific from the Middle-Pleistocene to present. The SST reconstructions are based on Mg/Ca ratios of planktic foraminifers and biomarker (alkenone) analyses. Based on preliminary and published data, a lower east–west SST gradient and colder SSTs in the central Pacific occurred during warmer periods. La Niña Modoki conditions apparently become more frequent with increasing CO2 conditions pointing at the likelihood that La Niña Modoki conditions will become more prevalent in the near future. Accordingly, an increase in precipitation on both sides of the Pacific realm could be expected.

Tsunami deposits are required to assess the long-term hazard of tsunamis, in particular in regions with a short and fragmented historical record. In the North Sea region, evidence of tsunamis is scarce. However, the Shetland Islands are an exception, as they provide abundant deposits of the Storegga tsunami c. 8150 cal. a BP, and more fragmented evidence of younger events ~5500 and ~1500 cal. a BP. Sediments of the youngest tsunami – the so-called Dury Voe event – are considered uncertain and have only been found at two sites so far, as thin landward fining and landward thinning sand sheets which are vertically confined by peat. Here, we present sedimentary evidence for a tsunami from the small coastal lake of Loch Flugarth, northern Mainland. Three gravity cores of up to 91 cm length were taken behind the barrier separating the lake from a shallow marine embayment. The cores show organic-rich background deposition with many sub-cm-scale sand layers, reflecting recurring storm overwash and a sediment source limited to the active beach and uppermost subtidal. A basal 13 cm-thick sand layer, dated to 426–787 cal. a CE based on 14C-AMS, 137Cs and Bayesian age-depth modelling, was found in all three cores. High-resolution grain-size analysis identified four normally graded sublayers with inversely graded traction carpets in the lower part of two sublayers. An organic-rich “mud” drape and “mud” cap, respectively, cover the upper two sublayers, which also contain small rip-up clasts. Grain-size distributions shows a difference between the basal sand layer and the thin storm layers, which are coarser and better sorted. Principal component analysis of XRF core scanning data also distinguishes both sand units, mostly driven by Zr, Fe and Ti in the basal sand. This, in combination with increased magnetic susceptibility, may be related to higher heavy mineral content reflecting an additional marine sediment source for the tsunami deposit. Based on reinterpretation of chronological data from the two published sites and the chronostratigraphy of the present study, the Dury Voe tsunami seems to be younger than previously estimated, i.e. closer to 1400–1300 cal. a BP. The source of the tsunami remains unclear. As there is no evidence for this event outside the Shetlands, the size of the tsunami is expected to be smaller than the Storegga tsunami, which affected most of the North Sea basin.

Synchronous or metachronous growth of multiple tumors (≥ 2) is found in up to 20% of meningioma patients. However, biological as well as histological features and prognosis are largely unexplored. Clinical and histological characteristics were retrospectively investigated in 95 patients harboring 226 multiple meningiomas (MMs) and compared with 135 cases of singular meningiomas (SM) using uni- and multivariate analyses. In MM, tumors occurred synchronously and metachronously in 62% and 38%, respectively. WHO grade was intra-individually constant in all but two MMs, and histological subtype varied in 13% of grade 1 tumors. MM occurred more commonly in convexity/parasagittal locations, while SM were more frequent at the skull base (p p = .014) and high-grade histology in MM were associated with a prolonged time to progression (p p ≥ .05, each). Multivariate analyses showed synchronous/metachronous meningioma growth (HR 4.50, 95% CI 2.26–8.96; p p = .224), but exponentially raised in patients with 3–4 (HR 3.25, 1.22–1.62; p = .018) and ≥ 5 tumors (HR 13.80, 4.06–46.96; p

About 25% of patients with intracranial meningioma display seizures at the time of initial presentation. Hence, identification of risk factors for preoperative seizures is crucial during perioperative care of meningioma patients.Associations of preoperative seizures with clinical, radiological and histological variables were analyzed in 945 patients (689 females, 73% and 256 males, 27%; median age: 58 years) who underwent surgery for primary diagnosed intracranial meningioma.Preoperative seizures were found in 189 patients (20%). In univariate analyses, male gender (OR: 1.91, 95%CI 1.37-2.68; p.001), grade II/III histology (OR: 2.24, 95%CI 1.46-3.46; p.001), brain invasion (OR: 2.59, 95%CI 1.45-4.63; p=001), non-skull base tumor location (OR: 3.07, 95%CI 2.13-4.41; p.001), heterogeneous contrast-enhancement (OR: 1.60, 95%CI 1.04-2.46; p=.031), intratumoral calcifications (OR: 1.91, 95%CI 1.17-3.10; p=.009), an irregular shape (OR: 2.07, 95%CI 1.32-3.26; p=.002) as well as tumor (OR: 1.01 per ccm, 95%CI 1.00-1.02; p=.001) and edema volumes (OR: 1.01 per ccm, 95%CI 1.00-1.01; p.001) were correlated with seizures. Semiology was not related to any of the analyzed variables (p.05, each). No associations were found between seizures and histological subtype of 832 grade I meningiomas (p=.391). In multivariate analyses, only non-skull base tumor location (OR: 3.12, 95%CI 1.74-5.59; p.001) and a rising peritumoral edema volume (OR: 1.01 per ccm, 95%CI 1.00-1.01; p.001) were identified as independent predictors for preoperative seizures.Several mostly radiological variables were identified as risk factors for epilepsy. However, multivariate analyses confirmed only peritumoral edema and non-skull base tumor location as independent predictors for preoperative seizures. None of the variables predicts semiology.

Risk factors to predict late-onset tumor recurrence in meningioma patients are urgently needed to schedule control intervals during long-term follow-up. We therefore analyzed the value of established risk factors for postoperative meningioma recurrence for the prediction of long-term prognosis. Correlations of clinical and histopathological variables with tumor relapse after 3, 5, and 10 years following microsurgery were analyzed in uni- and multivariate analyses, and compared to findings in the entire cohort. In the entire cohort (N = 1218), skull base location (HR: 1.51, 95%CI 1.05–2.16; p = .026), Simpson ≥ IV resections (HR: 2.41, 95%CI 1.52–3.84; p p p = .042) were independent risk factors for recurrence. Skull base location (HR: 1.92, 95%CI 1.17–3.17; p = .010 and HR: 2.02, 95%CI 1.04–3.95; p = .038) and high-grade histology (HR: 1.87, 95%CI 1.04–3.38; p = .038 and HR: 2.29, 95%CI 1.07–4.01; p = .034) but not subtotal resection (HR: 1.53, 95%CI .68–3.45; p = .303 and HR: 1.75, 95%CI .52–5.96; p = .369) remained correlated with recurrence after a recurrence-free follow-up of ≥ 3 and ≥ 5 years, respectively. Postoperative tumor volume was related with recurrence in general (p p > .05). In 147 patients with a follow-up of ≥ 10 years, ten recurrences occurred and were not correlated with any of the analyzed variables. Skull base tumor location and high-grade histology but not the extent of resection should be considered when scheduling the long-term follow-up after meningioma surgery. Recurrences ≥ 10 years after surgery are rare, and predictors are lacking.

Fusarium spp. can cause invasive infection with fatal outcomes in immunocompromised patients. Therefore, invasive fusariosis is rare after solid organ transplantation. For this reason, experience and management are limited to single published case reports.We report a 65-year-old female patient with disseminated brain abscesses caused by Fusarium after liver transplantation (LT). The patient underwent LT for secondary sclerosing cholangitis after acute respiratory distress syndrome (ARDS). After a complicated course with aneurysm and thrombosis of the hepatic artery, re-transplantation was performed after one month. Due to inadequate awakening response, cerebral imaging was performed, which showed multiple abscesses. The patient died shortly thereafter, and an autopsy showed fusariosis.Fusarium spp. führen bei immungeschwächten Patienten zu einer invasiven Infektion mit meist tödlichem Ausgang. Eine invasive Fusariose wird nach der Transplantation solider Organe jedoch seltener berichtet. Aus diesem Grund ist die Erfahrung und das Management dieses Infektes auf einzelne Fallberichte beschränkt.Wir berichten von einer 65-jährige Patientin, die nach einer Lebertransplantation (LT) disseminierte Hirnabszesse verursacht durch Fusarien entwickelte. Die Patientin unterzog sich einer LT aufgrund einer sekundär sklerosierender Cholangitis nach akutem Lungenversagen (ARDS). Nach einem komplizierten Verlauf mit Aneurysma und Thrombose der Leberarterie erfolgte nach einem Monat eine Re-Transplantation. Aufgrund der unzureichenden Aufwachreaktion wurde eine zerebrale Bildgebung durchgeführt, die multiple Abszesse zeigte. Die Patientin verstarb kurz darauf, in der Autopsie wurden Fusarien nachgewiesen.

Classification of the extent of resection into gross and subtotal resection (GTR and STR) after meningioma surgery is derived from the Simpson grading. Although utilized to indicate adjuvant treatment or study inclusion, conflicting definitions of STR in terms of designation of Simpson grade III resections exist. Correlations of Simpson grading and dichotomized scales (Simpson grades I–II vs ≥ III and grade I–III vs ≥ IV) with postoperative recurrence/progression were compared using Cox regression models. Predictive values were further compared by time-dependent receiver operating curve (tdROC) analyses. In 939 patients (28% males, 72% females) harboring WHO grade I (88%) and II/III (12%) meningiomas, Simpson grade I, II, III, IV, and V resections were achieved in 29%, 48%, 11%, 11%, and p = .003). The risk of recurrence/progression was increased after STR in both dichotomized scales but higher when subsuming Simpson grade ≥ IV than grade ≥ III resections (HR: 2.49, 95%CI 1.50–4.12; p p = .012). tdROC analyses showed moderate predictive values for the Simpson grading and significantly (p

Remote ischemic preconditioning (RIPC) protects the heart against myocardial ischemia/reperfusion (I/R) injury and recent work also suggested chronic remote ischemic conditioning (cRIPC) for cardiovascular protection. Based on current knowledge that systemic immunomodulatory effects of RIPC and the anti-inflammatory capacity of monocytes might be involved in cardiovascular protection, the aim of our study was to evaluate whether RIPC/cRIPC blood plasma is able to induce in-vitro angiogenesis, identify responsible factors and evaluate the effects of RIPC/cRIPC on cell surface characteristics of circulating monocytes. Eleven healthy volunteers were subjected to RIPC/cRIPC using a blood pressure cuff inflated to > 200 mmHg for 3 × 5 min on the upper arm. Plasma and peripheral blood monocytes were isolated before RIPC (Control), after 1 × RIPC (RIPC) and at the end of 1 week of daily RIPC (cRIPC) treatment. Plasma concentrations of potentially pro-angiogenic humoral factors (CXCL5, Growth hormone, IGFBP3, IL-1α, IL-6, Angiopoietin 2, VEGF, PECAM-1, sTie-2, IL-8, MCSF) were measured using custom made multiplex ELISA systems. Tube formation assays for evaluation of in-vitro angiogenesis were performed with donor plasma, monocyte conditioned culture media as well as IL-1α, CXCL5 and Growth hormone. The presence of CD14, CD16, Tie-2 and CCR2 was analyzed on monocytes by flow cytometry. Employing in-vitro tube formation assays, several parameters of angiogenesis were significantly increased by cRIPC plasma (number of nodes, P P P P P

Several factors contribute to Surinames particular vulnerability to the effects of climate change. It is dependent on fossil fuels, has forests liable to decay, fragile ecosystems, and its low-lying coastal area accounts for 87% of the population and most of the countrys economic activity. Many sectors are at risk of suffering losses and damage caused by gradual changes and extreme events related to climate change. For Suriname to develop sustainably, it should incorporate climate change and its effects into its decision-making process based on scientific- evidence. The State of the Climate Report analyzes Surinames historical climate (1990-2014) and provides climate projections for three time horizons (2020-2044, 2045-2069, 2070-2094) through two emissions scenarios (intermediate/ SSP2-4.5 and severe/ SSP5-8.5). The analysis focuses on changes in sea level, temperature, precipitation, relative humidity, and winds for the seven subnational locations of Paramaribo, Albina, Bigi Pan MUMA, Brokopondo, Kwamalasamutu, Tafelberg Natural Reserve, and Upper Tapanahony. The Report also analyzes climate risk for the countrys ten districts by examining the factors which increase their exposure and vulnerability on the four most important sectors affected by climate change: infrastructure, agriculture, water, and forestry, as well as examining the effects across the sectors. The State of the Climate provides essential inputs for Suriname to develop and update its climate change policies and targets. These policies and targets should serve as enablers for an adequate mainstreaming of climate change adaptation and resilience enhancement into day-to-day government operations.

Suriname is highly vulnerable to the effects of climate change. Among the factors that exacerbate its vulnerability are its dependency on fossil fuels, the degradation of important ecosystems (e.g., mangroves), and the fact that 87% of the population, and most of the countrys economic activity is located within the low-lying coastal area. Many sectors are at risk of suffering losses and damage caused by gradual changes and extreme events related to climate change. For Suriname to develop sustainably, it should incorporate climate change and its effects into its decision-making process based on scientific- evidence. The State of the Climate Report analyzes Surinames historical climate (1990-2014) and provides climate projections for three time horizons (2020-2044, 2045-2069, 2070-2094) through two emissions scenarios (intermediate/ SSP2-4.5 and severe/ SSP5-8.5). The analysis focuses on changes in sea level, temperature, precipitation, relative humidity, and winds for the seven subnational locations of Paramaribo, Albina, Bigi Pan MUMA, Brokopondo, Kwamalasamutu, Tafelberg Natural Reserve, and Upper Tapanahony. The Report also analyzes climate risk for the countrys ten districts by examining the factors which increase their exposure and vulnerability on the four most important sectors affected by climate change: infrastructure, agriculture, water, and forestry, as well as examining the effects across the sectors. The State of the Climate Report provides essential inputs for Suriname to develop and update its climate change policies and targets. These policies and targets should enable an adequate mainstreaming of climate change adaptation and resilience enhancementinto day-to-day government operations. It is expected that the Report will catalyze similar efforts in the future to improve decision-making by providing science-based evidence.

OBJECTIVEIdentification of risk factors for perioperative epilepsy remains crucial in the care of patients with meningioma. Moreover, associations of brain invasion with clinical and radiological variables have been largely unexplored. The authors hypothesized that invasion of the cortex and subsequent increased edema facilitate seizures, and they compared radiological data and perioperative seizures in patients with brain-invasive or noninvasive meningioma.METHODSCorrelations of brain invasion with tumor and edema volumes and preoperative and postoperative seizures were analyzed in univariate and multivariate analyses.RESULTSTotals of 108 (61%) females and 68 (39%) males with a median age of 60 years and harboring totals of 92 (52%) grade I, 79 (45%) grade II, and 5 (3%) grade III tumors were included. Brain invasion was found in 38 (22%) patients and was absent in 138 (78%) patients. The tumors were located at the convexity in 72 (41%) patients, at the falx cerebri in 26 (15%), at the skull base in 69 (39%), in the posterior fossa in 7 (4%), and in the ventricle in 2 (1%); the median tumor and edema volumes were 13.73 cm3 (range 0.81–162.22 cm3) and 1.38 cm3 (range 0.00–355.80 cm3), respectively. As expected, edema volume increased with rising tumor volume (p < 0.001). Brain invasion was independent of tumor volume (p = 0.176) but strongly correlated with edema volume (p < 0.001). The mean edema volume in noninvasive tumors was 33.0 cm3, but in invasive tumors, it was 130.7 cm3 (p = 0.008). The frequency of preoperative seizures was independent of the patients’ age, sex, and tumor location; however, the frequency was 32% (n = 12) in patients with invasive meningioma and 15% (n = 21) in those with noninvasive meningioma (p = 0.033). In contrast, the probability of detecting brain invasion microscopically was increased more than 2-fold in patients with a history of preoperative seizures (OR 2.57, 95% CI 1.13–5.88; p = 0.025). In univariate analyses, the rate of preoperative seizures correlated slightly with tumor volume (p = 0.049) but strongly with edema volume (p = 0.014), whereas seizure semiology was found to be independent of brain invasion (p = 0.211). In multivariate analyses adjusted for age, sex, tumor location, tumor and edema volumes, and WHO grade, rising tumor volume (OR 1.02, 95% CI 1.00–1.03; p = 0.042) and especially brain invasion (OR 5.26, 95% CI 1.52–18.15; p = 0.009) were identified as independent predictors of preoperative seizures. Nine (5%) patients developed new seizures within a median follow-up time of 15 months after surgery. Development of postoperative epilepsy was independent of all clinical variables, including Simpson grade (p = 0.133), tumor location (p = 0.936), brain invasion (p = 0.408), and preoperative edema volume (p = 0.081), but was correlated with increasing preoperative tumor volume (p = 0.004). Postoperative seizure-free rates were similar among patients with invasive and those with noninvasive meningioma (p = 0.372).CONCLUSIONSBrain invasion was identified as a new and strong predictor for preoperative, but not postoperative, seizures. Although also associated with increased peritumoral edema, seizures in patients with invasive meningioma might be facilitated substantially by cortical invasion itself. Consideration of seizures in consultations between the neurosurgeon and neuropathologist can improve the microscopic detection of brain invasion.

Severe storms, their extreme waves and surges pose the greatest natural hazard to the coasts of northwestern Europe, commonly resulting in infrastructural damages and high financial losses. Proxy records of past storminess are important for assessing future risks that may arise from storm surges and assessing whether storm activity has increased in recent decades. High-resolution records of North Atlantic storminess are generally limited to instrumental weather data or historical documentation of the past 50 to 200 years. Since the most destructive and severe storms passing over Europe originate in the North Atlantic, the Shetland Islands serve as a window to cyclogenesis in this region. In our research, we extracted lacustrine sediments of the coastal freshwater lake Loch of Flugarth on Mainland, Shetland Islands, that is separated from the ocean by a low sand and gravel barrier. A series of distinct sand layers intercalated in the otherwise fine-grained, organic-rich lake deposits and examined using particle-size analysis, microfossils, TOC and XRF, may represent storm overwash or aeolian transport mechanisms, both either pointing towards individual storm events or shorter phases of high storm activity. Based on radiocarbon data of some selected layers, the investigated sediment sequence covers ca. 1500 years and a Bayesian age-depth model is being established. In combination with a hydrodynamic wave model based on Delft3D-Flow, we simulate a critical threshold value at which waves may reach the lake to determine the sensitivity of the sedimentary archive. With the inclusion of historical documentation and observations, our multi-methodological approach aims at reaching a better understanding of the recurrence pattern of extreme storm events on the Shetland Islands over the last 1500 years. This implies further insights into the parameters driving extra-tropical storms in the wider region as well as the role and variability of the North Atlantic Oscillation across the targeted time frame.

ObjectiveTo determine whether B-cell presence in brainstem and white matter (WM) lesions is associated with poorer pathological and clinical characteristics in advanced MS autopsy cases.MethodsAutopsy tissue of 140 MS and 24 control cases and biopsy tissue of 24 patients with MS were examined for CD20+ B cells and CD138+ plasma cells. The presence of these cells was compared with pathological and clinical characteristics. In corresponding CSF and plasma, immunoglobulin (Ig) G ratio and oligoclonal band (OCB) patterns were determined. In a clinical cohort of 73 patients, the presence of OCBs was determined during follow-up and compared to status at diagnosis.ResultsIn 34% of active and 71% of mixed active/inactive lesions, B cells were absent, which correlated with less pronounced meningeal B-cell infiltration (p < 0.0001). The absence of B cells and plasma cells in brainstem and WM lesions was associated with a longer disease duration (p = 0.001), less frequent secondary progressive MS compared with relapsing and primary progressive MS (p < 0.0001 and p = 0.046, respectively), a lower proportion of mixed active/inactive lesions (p = 0.01), and less often perivascular T-cell clustering (p < 0.0001). Moreover, a lower CSF IgG ratio (p = 0.006) and more frequent absence of OCBs (p < 0.0001) were noted. In a clinical cohort, numbers of patients without OCBs in CSF were increased at follow-up (27.4%).ConclusionsThe absence of B cells is associated with a favorable clinical and pathological profile. This finding may reflect extremes of a continuum of genetic or environmental constitution, but also a regression of WM humoral immunopathology in the natural course of advanced MS.

In the semi-arid and arid regions of the Chilean Andes, meltwater from the cryosphere is a key resource for the local economy and population. In this setting, climate change and economic activities foster water scarcity and resource conflicts. The study presents a detailed glacier and rock glacier inventory for the Huasco valley (28&ndash, 29&deg, S) in northern Chile based on a multi-temporal remote sensing approach. The results indicate a glacier-covered area of 16.35 &plusmn, 3.06 km2 (n = 167) and, additionally, 50 rock glaciers covering an area of about 8.6 km2 in 2016. About 81% of the ice-bodies are smaller than 0.1 km2, and only four glaciers are larger than 1 km2. The change analysis reveals a more or less stable period between 1986 and 2000 and a drastic decline in the glacier-covered area by about 35% between 2000 and 2016. The detailed assessment of six subregions indicates a more pronounced glacier decrease in the vicinity of the Pascua Lama mining project.

Seizures after meningioma surgery are common, with a distinct impact on postoperative life quality. Sufficient risk factors for seizure development are sparsely known but needed to improve perioperative patient counseling and, eventually, antiepileptic treatment.Correlations between clinical, radiological and histological variables and the onset of new seizures following surgery for initially diagnosed cranial meningioma were retrospectively analyzed in uni- and multivariate analyses.752 preoperatively seizure-naïve patients (569 females, 76 % and 183 males, 24 %) with a median age of 57 years were included. Postoperative seizures occurred in 69 cases (9 %). In univariate analyses, seizures were correlated with preoperative Karnofsky Score80 (OR: 1.91, 95 % CI 1.01-3.59; p = .045), convexity/parasagittal tumor location (OR: 1.77, 95 % CI 1.06-2.95; p = .030), heterogenous contrast-enhancement of the tumor (OR: 2.24, 95 % CI 1.14-4.39; p = .019) and intratumoral calcifications (OR: 3.35, 95 % CI 1.59-7.05; p = .001). Multivariable analyses revealed age at the time of surgery (OR: 1.04, 95 % CI 1.01-1.07; p = .009) and intratumoral calcifications on preoperative imaging (OR: 3.70, 95 % CI 1.73-7.92; p = .001) as risk factors for postoperative seizures. Based on multivariate analyses, a score for discrimination of patients at low (3 %), intermediate (11 %) and high risk (17 %) of postoperative seizures (AUC: 0.7, p.001) was conducted. In subgroup analyses, postoperative hemorrhage (OR: 2.90, 95 % CI 1.13-7.46; p = .028) and hydrocephalus (OR: 3.65, 95 % CI 1.48-9.01; p = .005) were correlated with postoperative seizures.Risk factors for postoperative seizures after meningioma surgery are sparse and can be basically taken from preoperative imaging. Among surgical complications, postoperative hemorrhage and hydrocephalus are strong seizure predictors.

OBJECTIVE In meningiomas, the Simpson grading system is applied to estimate the risk of postoperative recurrence, but might suffer from bias and limited overview of the resection cavity. In contrast, the value of the postoperative tumor volume as an objective predictor of recurrence is largely unexplored. The objective of this study was to compare the predictive value of residual tumor volume with the intraoperatively assessed extent of resection (EOR). METHODS The Simpson grade was determined in 939 patients after surgery for initially diagnosed intracranial meningioma. Tumor volume was measured on initial postoperative MRI within 6 months after surgery. Correlation between both variables and recurrence was compared using a tree-structured Cox regression model. RESULTS Recurrence correlated with Simpson grading (p = 0.003). In 423 patients (45%) with available imaging, residual tumor volume covered a broad range (0–78.5 cm3). MRI revealed tumor remnants in 8% after gross-total resection (Simpson grade I–III, range 0.12–33.5 cm3) with a Cohen’s kappa coefficient of 0.7153. Postoperative tumor volume was correlated with recurrence in univariate analysis (HR 1.05 per cm3, 95% CI 1.02–1.08 per cm3, p < 0.001). A tree-structured Cox regression model revealed any postoperative tumor volume > 0 cm3 as a critical cutoff value for the prediction of relapse. Multivariate analysis confirmed the postoperative tumor volume (HR 1.05, p < 0.001) but not the Simpson grading (p = 0.398) as a predictor for recurrence. CONCLUSIONS EOR according to Simpson grading was overrated in 8% of tumors compared to postoperative imaging. Because the predictive value of postoperative imaging is superior to the Simpson grade, any residual tumor should be carefully considered during postoperative care of meningioma patients.

The usefulness of 5-aminolevulinic acid (5-ALA)–mediated fluorescence-guided surgery (FGS) in meningiomas is intensely discussed. However, data about kinetics of 5-ALA and protoporphyrin (Pp) IX in meningiomas are lacking. As the first study so far, we performed longitudinal intraoperative real-time ex situ measurements of fluorescence intensity and PpIX concentrations during FGS of ten benign and two atypical meningiomas. Kinetics were subsequently compared with data from 229 glioblastomas. Spectroscopy revealed fluorescence (median 2945.65 a.u.) and PpIX accumulation (median 18.31 μg/ml) in all 43 analyzed samples. Fluorescence intensity (2961.50 a.u. vs 118.41 a.u.; p

Risk factors for prediction of prognosis in meningiomas derivable from routine preoperative magnetic resonance imaging (pMRI) remain elusive. Correlations of tumor and edema volume, disruption of the arachnoid layer, heterogeneity of contrast enhancement, enhancement of the capsule, T2-intensity, tumor shape, and calcifications on pMRI with tumor recurrence and high-grade (WHO grade II/III) histology were analyzed in 565 patients who underwent surgery for WHO grade I (N = 516, 91%) or II/III (high-grade histology, N = 49, 9%) meningioma between 1991 and 2018. Edema volume (OR, 1.00; p = 0.003), heterogeneous contrast enhancement (OR, 3.10; p p = 0.015) were associated with high-grade histology. Multivariate analyses confirmed edema volume (OR, 1.00; p = 0.037) and heterogeneous contrast enhancement (OR, 2.51; p = 0.014) as risk factors for high-grade histology. Tumor volume (HR, 1.01; p = 0.045), disruption of the arachnoid layer (HR, 2.50; p = 0.003), heterogeneous contrast enhancement (HR, 2.05; p = 0.007), and an irregular tumor shape (HR, 2.57; p = 0.001) were correlated with recurrence. Multivariate analyses confirmed tumor volume (HR, 1.01; p = 0.032) and disruption of the arachnoid layer (HR, 2.44; p = 0.013) as risk factors for recurrence, independent of histology. Subgroup analyses revealed disruption of the arachnoid layer (HR, 9.41; p p = 0.001). Routine pMRI contains relevant information about the risk of recurrence or high-grade histology of meningioma patients. Loss of integrity of the arachnoid layer on MRI had a higher prognostic value than the WHO grading, and underlying histological or molecular alterations remain to be determined.

Multiple sclerosis (MS) is the most frequent demyelinating disease in young adults and despite significant advances in immunotherapy, disease progression still cannot be prevented. Promotion of remyelination, an endogenous repair mechanism resulting in the formation of new myelin sheaths around demyelinated axons, represents a promising new treatment approach. However, remyelination frequently fails in MS lesions, which can in part be attributed to impaired differentiation of oligodendroglial progenitor cells into mature, myelinating oligodendrocytes. The reasons for impaired oligodendroglial differentiation and defective remyelination in MS are currently unknown. To determine whether intrinsic oligodendroglial factors contribute to impaired remyelination in relapsing–remitting MS (RRMS), we compared induced pluripotent stem cell-derived oligodendrocytes (hiOL) from RRMS patients and controls, among them two monozygous twin pairs discordant for MS. We found that hiOL from RRMS patients and controls were virtually indistinguishable with respect to remyelination-associated functions and proteomic composition. However, while analyzing the effect of extrinsic factors we discovered that supernatants of activated peripheral blood mononuclear cells (PBMCs) significantly inhibit oligodendroglial differentiation. In particular, we identified CD4+ T cells as mediators of impaired oligodendroglial differentiation; at least partly due to interferon-gamma secretion. Additionally, we observed that blocked oligodendroglial differentiation induced by PBMC supernatants could not be restored by application of oligodendroglial differentiation promoting drugs, whereas treatment of PBMCs with the immunomodulatory drug teriflunomide prior to supernatant collection partly rescued oligodendroglial differentiation. In summary, these data indicate that the oligodendroglial differentiation block is not due to intrinsic oligodendroglial factors but rather caused by the inflammatory environment in RRMS lesions which underlines the need for drug screening approaches taking the inflammatory environment into account. Combined, these findings may contribute to the development of new remyelination promoting strategies. Electronic supplementary material The online version of this article (10.1007/s00401-020-02217-8) contains supplementary material, which is available to authorized users.

This paper combines long-term state-of-the-art climate projections and indices to provide detailed insights into the future climate of Suriname to facilitate comprehensive information of areas and sectors at high climate risk for political decision-making. The study analyses Suriname’s historical climate (1990–2014) and provides climate projections for three time horizons (2020–2044, 2045–2069, 2070–2094) and two emissions scenarios (intermediate/SSP2-4.5 and severe/SSP5-8.5). Coupled Model Intercomparison Project (CMIP6) modeling is used to analyze changes in sea level, temperature, precipitation, relative humidity, and winds. In addition, risk impact chains were produced for the country’s four most important socio-economic sectors: agriculture and fisheries, forestry, water, and infrastructure. Results show the temperature is expected to increase for all regions and timeframes, reaching warming up to 6 °C in the southern region in the long-term future (2070–2094). Projections point towards a reduction in precipitation in the southwest and coastal regions and a rise in mean sea level. Regarding risk, Paramaribo and Wanica face the highest climate risk. Coronie and Nickerie face the least climate risk. These regions remain the most and least vulnerable in both the SSP2-4.5 and SSP5-8.5 scenarios, but overall values of their risk indices increase substantially over time.

Background There is an increasing interest in local tumor ablative treatment modalities that induce immunogenic cell death and the generation of antitumor immune responses. Methods We report six recurrent glioblastoma patients who were treated with intracavitary thermotherapy after coating the resection cavity wall with superparamagnetic iron oxide nanoparticles (“NanoPaste” technique). Patients underwent six 1-h hyperthermia sessions in an alternating magnetic field and, if possible, received concurrent fractionated radiotherapy at a dose of 39.6 Gy. Results There were no major side effects during active treatment. However, after 2–5 months, patients developed increasing clinical symptoms. CT scans showed tumor flare reactions with prominent edema around nanoparticle deposits. Patients were treated with dexamethasone and, if necessary, underwent re-surgery to remove nanoparticles. Histopathology revealed sustained necrosis directly adjacent to aggregated nanoparticles without evidence for tumor activity. Immunohistochemistry showed upregulation of Caspase-3 and heat shock protein 70, prominent infiltration of macrophages with ingested nanoparticles and CD3+ T-cells. Flow cytometric analysis of freshly prepared tumor cell suspensions revealed increased intracellular ratios of IFN-γ to IL-4 in CD4+ and CD8+ memory T cells, and activation of tumor-associated myeloid cells and microglia with upregulation of HLA-DR and PD-L1. Two patients had long-lasting treatment responses > 23 months without receiving any further therapy. Conclusion Intracavitary thermotherapy combined with radiotherapy can induce a prominent inflammatory reaction around the resection cavity which might trigger potent antitumor immune responses possibly leading to long-term stabilization of recurrent GBM patients. These results warrant further investigations in a prospective phase-I trial.

Brain invasion (BI) in meningiomas impacts WHO grading and therefore adjuvant treatment. However, BI is rare and neurosurgical sampling and neuropathological analyses are not standardised. Moreover, associations with imaging findings are sparsely known. Associations between BI and findings on preoperative MRI were investigated in 617 meningioma patients. BI was strongly correlated with other high-grade criteria (p.05, each). High-grade histology (p=.033) but not BI (p=.354) was associated with tumour location. Irregular tumour shape (OR: 3.33, 95%CI 1.33-8.30; p=.007), heterogeneous contrast enhancement (OR: 2.82, 95%CI 1.19-6.70; p=.015) and peritumoural edema (OR: 1.005 per ccm, 95%CI 1.001-1.008); p=.011) were associated with BI. Multivariable analyses identified only increasing edema volume (OR: 1.005 per ccm, 95%CI 1.002-1.009; p=.010) as a predictor for BI, independent of other histopathological high-grade criteria. We finally provide a new model to estimate the risk of BI using routine preoperative MRI. Several imaging characteristics were identified as predictors for BI. Consideration in clinical routine can increase the accuracy of the detection in neuropathological analyses.

We analyzed the applicability of the Simpson grading system to estimate the risk of tumor recurrence after microsurgery for recurrent meningiomas.Correlations between the Simpson grade and the extent of resection (EOR) (gross total resection [Simpson grade I and II] vs. subtotal resection [Simpson grade ≥III]) with tumor relapse after microsurgery for meningioma recurrence were investigated compared with the findings in primary diagnosed tumors. Location-specific differences were further elucidated in subgroup analyses.A total of 829 individuals (88% in group A) with primary diagnosed meningioma and 109 patients with first postoperative recurrence (12% in group B) who underwent surgery were included. In group A, both Simpson grade (P = 0.003) and EOR (P0.001) correlated strongly with recurrence. In group B, Simpson grade correlated with tumor location (P = 0.030), and the risk of subtotal resection was greater in the posterior fossa (odds ratio, 5.26; P = 0.018) and skull base (odds ratio, 6.16; P = 0.002) meningiomas. Older age at tumor relapse (hazard ratio [HR], 1.05; P = 0.001), male sex (HR, 2.19; P = 0.02), and grade 2/3 histologic findings (HR, 2.18; P = 0.02). However, neither the Simpson grade nor dichotomized EOR correlated with further tumor recurrence. The frequency of postoperative complications was similar in both groups.Surgery for recurrent meningiomas is not generally associated with an increased risk of postoperative complications compared with resection of primary diagnosed tumors. However, the Simpson grade and EOR in recurrent meningiomas correlated poorly with further tumor relapse. The lower prognostic value of the tumor remnants left behind during microsurgery for recurrent meningiomas should be considered when operating on lesions that can be surgically challenging.

Although the majority of surgeries for spinal meningiomas are performed in geriatric patients, age-related analyzes of preoperative symptoms and functional outcome are sparse. Clinical, neuropathological and radiological data of 88 patients who underwent surgery for spinal meningiomas were reviewed. Correlations between the patients’ age and preoperative symptoms as well as functional outcome were investigated. 14 males (16%) and 74 females (84%) with a median age of 67 years were included. Age at the time of surgery was independent of the tumor location and volume, intra-/extradural tumor location, spinal cord compression or signal change on T2-weighted MRI (p > 0.05, each). Preoperative McCormick score (p = 0.001), motor (p = 0.005) and sensory (p = 0.025) deficits and incontinence (p = 0.010) increased, while frequency of radicular pain decreased with increasing age (p = 0.020). Multivariate analyses confirmed an increasing risk of motor (OR: 1.05, p = 0.017) and, with borderline significance, of sensory deficits (OR: 1.04, 95%CI 1.00–1.10; p = 0.056) with rising age. Simpson grades I, II, III and IV were achieved in 12 (14%), 54 (64%), 14 (17%) and 4 (5%) individuals, respectively. Only 3 of 12 patients (25%) with perioperative complications were younger than 65 years. Rising age was associated with improvement of motor (p = 0.006) and sensory deficits (p = 0.045). In multivariate analyzes, probability of improvement of preoperative motor weakness (OR = 1.05, p = 0.031) and sensory deficits (OR = 1.07, p = 0.014) increased with rising age. Despite more frequent preoperative neurological deficits, older patients with spinal meningiomas recover most noticeably after surgery. However, stratification of the medical condition is urgent to reduce complications.

With the release of the 2016 edition of the World Health Organization (WHO) Classification of Central Nervous System Tumors, brain invasion in meningiomas has been added as a stand-alone criterion for atypia and can therefore impact grading and indirectly adjuvant therapy. Regarding this rising clinical importance, we have reviewed the current knowledge about brain invasion with emphasis on its implications on current and future clinical practice. We found various definitions of brain invasion and approaches for evaluation in surgically obtained specimens described over the past decades. This heterogeneity is reflected by weak correlation with prognosis and remains controversial. Similarly, associated clinical factors are largely unknown. Preoperative, imaging-guided detection of brain invasion is unspecific, and intraoperative assessment using standard and new high-magnification microscopic techniques remains imprecise. Despite the increasing knowledge about molecular alterations of the tumor/ brain surface, pharmacotherapeutic options targeting brain invasive meningiomas are lacking. Finally, we summarize the impact of brain invasion on histopathological grading in the WHO classifications of brain tumors since 1979.In conclusion, standardized neurosurgical sampling and neuropathological analyses could improve diagnostic reliability and reproducibility of future studies. Further research is needed to improve pre- and intraoperative visualization of brain invasion and to develop adjuvant, targeted therapies.

OBJECTIVE The purpose of this study was to compare long-term prognosis after meningioma surgery in elderly and younger patients as well as to compare survival of elderly patients with surgically treated meningioma to survival rates for the general population. METHODS Five hundred meningioma patients (median follow-up 90 months) who underwent surgery between 1994 and 2009 were subdivided into “elderly” (age ≥ 65 years, n = 162) and “younger” (age < 65 years, n = 338) groups for uni- and multivariate analyses. Mortality was compared with rates for the age- and sex-matched general population. RESULTS The median age at diagnosis was 71 in the elderly group and 51 years in the younger group. Sex, intracranial tumor location, grade of resection, radiotherapy, and histopathological subtypes were similar in the 2 groups. High-grade (WHO Grades II and III) and spinal tumors were more common in older patients than in younger patients (15% vs 8%, p = 0.017, and 12% vs 4%, p = 0.001, respectively). The progression-free interval (PFI) was similar in the 2 groups, whereas mortality at 3 months after surgery was higher and median overall survival (OS) was shorter in older patients (7%, 191 months) than in younger patients (1%, median not reached; HR 4.9, 95% CI 2.75–8.74; p < 0.001). Otherwise, the median OS in elderly patients did not differ from the anticipated general life expectancy (HR 1.03, 95% CI 0.70–1.50; p = 0.886). Within the older patient group, PFI was lower in patients with high-grade meningiomas (HR 24.74, 95% CI 4.23–144.66; p < 0.001) and after subtotal resection (HR 10.57, 95% CI 2.23–50.05; p = 0.003). Although extent of resection was independent of perioperative mortality, the median OS was longer after gross-total resection than after subtotal resection (HR 2.7, 95% CI 1.09–6.69; p = 0.032). CONCLUSIONS Elderly patients with surgically treated meningioma do not suffer from impaired survival compared with the age-matched general population, and their PFI is similar to that of younger meningioma patients. These data help mitigate fears concerning surgical treatment of elderly patients in an aging society.

Amyloidomas are rare amyloid-containing lesions, which may also occur in the central nervous system. Etiology, pathogenesis and clinical course are poorly understood. To gain more insight into the biology of cerebral amyloidoma, they aimed to characterize its histopathological, molecular and clinical features in a retrospective series of seven patients. FFPE tissue specimens were examined using immunohistochemistry, chromogenic in situ hybridization (CISH) for light chains kappa and lambda as well as an IgH gene clonality analysis. Follow-up information was gathered by reviewing patient records and imaging results. Median age of the three males and four females was 50 years (range: 35-53 years). All cerebral amyloidomas were located supratentorially and were classified as lambda light chain amyloidosis (AL-λ; n = 6) and kappa light chain amyloidosis (AL-κ; n = 1) on immunohistochemistry and CISH. B-cell clonality was confirmed by IgH gene clonality assay in all cases examined. After a median follow-up of 21 months, all patients were alive and showed stable disease. No progression to systemic disease was observed. In conclusion, their data suggest that cerebral amyloidoma is a local disease characterized by B-cell clonality and associated with a stable clinical course.

Despite considerable advances in preoperative and intraoperative imaging and neuronavigation, resection of thalamic gliomas remains challenging. Although both endoscopic biopsy and third ventriculostomy (ETV) for the treatment of secondary hydrocephalus are commonly performed, endoscopic resection of thalamic gliomas has been very sparsely described. We report and illustrate the surgical procedure and patient’s outcome after full endoscopic resection of a thalamic glioma and to discuss this approach as an alternative to open microsurgery. In 2016, a 56-year-old woman presented with disorientation, dysphasia and right facial hypaesthesia in our department. Cranial magnetic resonance imaging revealed a left thalamic lesion and subsequent hydrocephalus. Initially, hydrocephalus was treated by ETV but forceps biopsy was not diagnostic. However, metabolism in 18F-fluoroethyl-L-tyrosine positron emission tomography indicated glioma. Subsequently, endoscopic and neuronavigation-guided tumour resection was performed using a

In this feasibility study, a novel catheter prototype for laser thrombolysis under the guidance of optical coherence tomography (OCT) was designed and evaluated in a preclinical model. Human arteries and veins were integrated into a physiological flow model and occluded with thrombi made from the Chandler Loop. There were four experimental groups: placebo, 20 mg alteplase, laser, 20 mg alteplase + laser. The extent of thrombolysis was analyzed by weighing, OCT imaging and relative thrombus size. In the alteplase group, thrombus size decreased to 0.250 ± 0.036 g (p < 0.0001) and 14.495 ± 0.526 mm2 (p < 0.0001) at 60 min. The relative thrombus size decreased to 73.6 ± 4.1% at 60 min (p < 0.0001). In the laser group, thrombus size decreased significantly to 0.145 ± 0.028 g (p < 0.0001) and 11.559 ± 1.034 mm2 (p < 0.0001). In the alteplase + laser group, thrombus size decreased significantly (0.051 ± 0.026 g; p < 0.0001; 9.622 ± 0.582 mm2; p < 0.0001; 47.4 ± 6.1%; p < 0.0001) in contrast to sole alteplase and laser application. The reproducibility and accuracy of the OCT imaging was high (SD

Background Remote ischemic preconditioning (RIPC) is a phenomenon, whereby repeated, non-lethal episodes of ischemia to an organ or limb exert protection against ischemia–reperfusion (I/R) injury in distant organs. Despite intensive research, there is still an apparent lack of knowledge concerning the RIPC-mediated mechanisms, especially in the intestine. Aim of this study was to evaluate possible protective effects RIPC on intestinal I/R injury. Methods Thirty rats were randomly assigned to four groups: I/R; I/R + RIPC; Sham; Sham + RIPC. Animals were anesthetized and the superior mesenteric artery was clamped for 30 min, followed by 60 min of reperfusion. RIPC-treated rats received 3 × 5 min of bilateral hindlimb I/R prior to surgery, sham groups obtained laparotomy without clamping. After I/R injury serum/tissue was analyzed for: Mucosal damage, Caspase-3/7 activity, expression of cell stress proteins, hydrogen peroxide (H2O2) and malondialdehyde (MDA) production, Hypoxia-inducible factor-1α (HIF-1α) protein expression and matrix metalloproteinase (MMP) activity. Results Intestinal I/R resulted in increased mucosal injury (P